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1.
Nutr Metab Cardiovasc Dis ; 28(4): 402-410, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29499850

RESUMO

BACKGROUND AND AIMS: Alterations to one-carbon metabolism, especially elevated plasma homocysteine (Hcy), have been suggested to be both a cause and a consequence of the metabolic syndrome (MS). A deeper understanding of the role of other one-carbon metabolites in MS, including s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH), and the methylation capacity index (SAM:SAH ratio) is required. METHODS AND RESULTS: 118 men and women with MS-risk factors were included in this cross-sectional study and cardiometabolic outcomes along with markers of one-carbon metabolism, including fasting plasma SAM, SAH, Hcy and vitamin B12 concentrations, were analysed. Multiple linear regression models were also used to examine the association between plasma one-carbon metabolites and cardiometabolic health features. We found that fasting plasma concentrations of Hcy, SAM and SAH were all positively correlated with markers of adiposity, including BMI (increase in BMI per 1-SD increase in one-carbon metabolite: 0.92 kg/m2 95% CI (0.28; 1.56), p = 0.005; 0.81 (0.15; 1.47), p = 0.02; 0.67 (-0.01; 1.36), p = 0.05, respectively). Hcy, but not SAM, SAH or SAM:SAH ratio was associated with BMI and body fat percentage after mutual adjustments. SAM concentrations were associated with higher fasting insulin (9.5% 95% CI (0.3; 19.5) per SD increase in SAM, p = 0.04), HOMA-IR (10.8% (0.8; 21.9), p = 0.03) and TNF-α (11.8% (5.0; 19.0), p < 0.001). CONCLUSION: We found little evidence for associations between SAM:SAH ratio and cardiometabolic variables, but higher plasma concentrations of SAM, SAH and Hcy are related to an overall higher risk of metabolic dysfunctions. The studies were registered at www.clinicaltrials.gov (NCT01719913 &NCT01731366).


Assuntos
Síndrome Metabólica/sangue , S-Adenosil-Homocisteína/sangue , S-Adenosilmetionina/sangue , Adiposidade , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Estudos Transversais , Jejum/sangue , Feminino , Nível de Saúde , Humanos , Mediadores da Inflamação/sangue , Insulina/sangue , Resistência à Insulina , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Vitamina B 12/sangue , Adulto Jovem
2.
Nutr J ; 16(1): 44, 2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28705254

RESUMO

BACKGROUND: Severe acute malnutrition (SAM) has been associated with low polyunsaturated fatty acid (PUFA) status. However, investigations regarding PUFA status and correlates in children with moderate acute malnutrition (MAM) from low-income countries are scarce. The aim of this study was to describe whole-blood PUFA levels in children with moderate acute malnutrition (MAM) and to identify correlates of PUFAs. METHODS: We conducted a cross-sectional study using baseline data from a prospective nutritional intervention trial among 1609 children with MAM aged 6-23 months in Burkina Faso,West Africa. Whole-blood PUFAs were measured by gas chromatography and expressed as percent of total whole-blood fatty acids (FA%). Potential correlates of PUFAs including infection, inflammation, hemoglobin, anthropometry (difference between children diagnosed as having MAM based on low mid-upper-arm-circumference (MUAC) only, low MUAC and weight-for-height z-score (WHZ), or low WHZ only) and diet were assessed by linear regression adjusted for age and sex. RESULTS: Children with MAM had low concentrations of whole-blood PUFAs, particularly n-3 PUFAs. Moreover, children diagnosed with MAM based only on low MUAC had 0.32 (95% confidence interval (CI), 0.14; 0.50) and 0.40 (95% CI, 0.16; 0.63) FA% lower arachidonic acid (AA) than those recruited based on both low WHZ as well as low MUAC and those recruited with low WHZ only, respectively. Infection and inflammation were associated with low levels of all long-chain (LC)-PUFAs, while hemoglobin was positively associated with whole-blood LC-PUFAs. CONCLUSION: While PUFA deficiency was not a general problem, overall whole-blood PUFA concentrations, especially of n-3 PUFAs, were low. Infection, inflammation, hemoglobin, anthropometry and diet were correlates of PUFAs concentrations in children with MAM. TRIAL REGISTRATION: The trial is registered at http://www.isrctn.com ( ISRCTN42569496 ).


Assuntos
Ácidos Graxos Insaturados/sangue , Desnutrição/tratamento farmacológico , Desnutrição/epidemiologia , Antropometria , Burkina Faso/epidemiologia , Proteína C-Reativa/metabolismo , Criança , Estudos Transversais , Dieta , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos Insaturados/deficiência , Feminino , Hemoglobinas/metabolismo , Humanos , Lactente , Masculino , Morbidade , Avaliação Nutricional , Orosomucoide/metabolismo , Fatores Socioeconômicos
3.
Br J Nutr ; 116(12): 2082-2090, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28065179

RESUMO

Dietary long-chain n-3 PUFA (n-3 LCPUFA) in infancy may have long-term effects on lifestyle disease risk. The present follow-up study investigated whether maternal fish oil (FO) supplementation during lactation affected growth and blood pressure in adolescents and whether the effects differed between boys and girls. Mother-infant pairs (n 103) completed a randomised controlled trial with FO (1·5 g/d n-3 LCPUFA) or olive oil (OO) supplements during the first 4 months of lactation; forty-seven mother-infant pairs with high fish intake were followed-up for 4 months as the reference group. We also followed-up 100 children with assessment of growth, blood pressure, diet by FFQ and physical activity by 7-d accelerometry at 13·5 (sd 0·4) years of age. Dried whole-blood fatty acid composition was analysed in a subgroup (n 49). At 13 years of age, whole-blood n-3 LCPUFA, diet, physical activity and body composition did not differ between the three groups. The children from the FO group were 3·4 (95 % CI 0·2, 6·6) cm shorter (P=0·035) than those from the OO group, and tended to have less advanced puberty (P=0·068), which explained the difference in height. There was a sex-specific effect on diastolic blood pressure (P sex×group=0·020), which was driven by a 3·9 (95 % CI 0·2, 7·5) mmHg higher diastolic blood pressure in the FO compared with the OO group among boys only (P=0·041). Our results indicate that early n-3 LCPUFA intake may reduce height in early adolescence due to a delay in pubertal maturation and increase blood pressure specifically in boys, thereby tending to counteract existing sex differences.


Assuntos
Desenvolvimento Infantil , Suplementos Nutricionais/efeitos adversos , Óleos de Peixe/efeitos adversos , Transtornos do Crescimento/etiologia , Lactação , Fenômenos Fisiológicos da Nutrição Materna , Pré-Hipertensão/etiologia , Adolescente , Desenvolvimento do Adolescente , Adulto , Estatura , Criança , Dinamarca/epidemiologia , Método Duplo-Cego , Exercício Físico , Feminino , Seguimentos , Transtornos do Crescimento/epidemiologia , Humanos , Masculino , Pré-Hipertensão/epidemiologia , Puberdade Tardia/epidemiologia , Puberdade Tardia/etiologia , Risco , Alimentos Marinhos , Fatores Sexuais
4.
J Consult Clin Psychol ; 92(7): 410-421, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39190445

RESUMO

OBJECTIVE: The aim of this study was to investigate a sequence of associations between clients' pretreatment attachment style, the development of individuated-secure attachment to the therapist (i.e., therapeutic attachment), and the experience of increased comfort with emotional closeness (growing engagement) or independence (growing autonomy) in therapy. Moreover, the study explored whether clients' experience of growing engagement or growing autonomy was associated with a change in interpersonal problems at the end of therapy. METHOD: Three hundred thirty adult clients (mean age 40.2, 75% female) were seen by 44 therapists in individual psychotherapy. The associations between pretreatment attachment insecurity measured on the Experiences in Close Relationships scale, repeated measures of therapeutic attachment measured on the Client Attachment to Therapist Scale, repeated measures of a growing engagement or growing autonomy measured on the Therapeutic Distance Scale, and pre-post measures of interpersonal problems measured on the Inventory for Interpersonal Problems were analyzed using multilevel modeling. Two types of therapeutic attachment were estimated, one controlling for anxious attachment characteristics and one for avoidant. RESULTS: Significant associations between higher levels of therapeutic attachment controlled for avoidant attachment characteristics and lower levels of growing autonomy in therapy were found. Moreover, higher levels of growing engagement in therapy and higher levels of therapeutic attachment controlled for anxious attachment characteristics were associated with a decrease in interpersonal problems at the end of therapy. CONCLUSIONS: Distinct types of therapeutic attachment may exert different influences on the process and outcome of therapy. Furthermore, therapists' attunement to clients' specific attachment needs in therapy may enhance interpersonal outcomes of treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Apego ao Objeto , Relações Profissional-Paciente , Psicoterapia , Humanos , Feminino , Masculino , Adulto , Psicoterapia/métodos , Pessoa de Meia-Idade , Relações Interpessoais , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Resultado do Tratamento
5.
Clin Exp Allergy ; 43(12): 1384-94, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24118234

RESUMO

BACKGROUND: We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. OBJECTIVE: The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. METHODS: Pregnant women from eastern Denmark were invited during 2008-2010 to a novel unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high-dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze. RESULTS: Seven hundred and thirty-eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over-representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit. CONCLUSIONS: The COPSAC2010 birth cohort study provides longitudinal clinical follow-up with highly specific end-points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle-related chronic inflammatory disorders such as asthma.


Assuntos
Eczema/etiologia , Hipersensibilidade/etiologia , Fenótipo , Adulto , Asma/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca , Suplementos Nutricionais , Eczema/prevenção & controle , Feminino , Óleos de Peixe/administração & dosagem , Humanos , Hipersensibilidade/prevenção & controle , Lactente , Recém-Nascido , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Estudos Longitudinais , Masculino , Exposição Materna , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fatores de Risco , Inquéritos e Questionários , Vitamina D/administração & dosagem
6.
Artigo em Inglês | MEDLINE | ID: mdl-35085895

RESUMO

Long-chain n-3 fatty acids (n-3 LCPUFA) may prevent chemotherapy-induced hyperlipidemia in children with acute lymphoblastic leukemia (ALL). However, compliance could be a problem and intake-biomarker correlations may be affected by bodyweight and blood transfusions. We assessed whole blood n-3 LCPUFA three times during the first 83 days of treatment in six 1-17-year-old children with ALL, who received 2.4-4.9 g/d n-3 LCPUFA depending on bodyweight. Mean compliance was 73%, which resulted in a 2.5-fold increase in blood n-3 LCPUFA irrespective of blood transfusions. The correlation between relative blood content of n-3 LCPUFA and intake in g/d across the study period was strong (r=0.76, p=0.001). When n-3 LCPUFA was expressed in absolute concentrations and intake per kg bodyweight the correlation decreased (r=0.39, p=0.164) and was driven by baseline values. Thus, relative content of n-3 LCPUFA in blood reflects fish oil compliance in children with ALL despite blood transfusions and differences in bodyweight.


Assuntos
Ácidos Graxos Ômega-3 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Suplementos Nutricionais , Ácidos Graxos , Óleos de Peixe , Humanos , Projetos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
7.
Eur J Clin Nutr ; 70(10): 1155-1161, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27302673

RESUMO

BACKGROUND/OBJECTIVES: We previously found that the OPUS School Meal Study improved reading and increased errors related to inattention and impulsivity. This study explored whether the cognitive effects differed according to gender, household education and reading proficiency at baseline. SUBJECTS/METHODS: This is a cluster-randomised cross-over trial comparing Nordic school meals with packed lunch from home (control) for 3 months each among 834 children aged 8 to 11 years. At baseline and at the end of each dietary period, we assessed children's performance in reading, mathematics and the d2-test of attention. Interactions were evaluated using mixed models. Analyses included 739 children. RESULTS: At baseline, boys and children from households without academic education were poorer readers and had a higher d2-error%. Effects on dietary intake were similar in subgroups. However, the effect of the intervention on test outcomes was stronger in boys, in children from households with academic education and in children with normal/good baseline reading proficiency. Overall, this resulted in increased socioeconomic inequality in reading performance and reduced inequality in impulsivity. Contrary to this, the gender difference decreased in reading and increased in impulsivity. Finally, the gap between poor and normal/good readers was increased in reading and decreased for d2-error%. CONCLUSIONS: The effects of healthy school meals on reading, impulsivity and inattention were modified by gender, household education and baseline reading proficiency. The differential effects might be related to environmental aspects of the intervention and deserves to be investigated further in future school meal trials.


Assuntos
Cognição/fisiologia , Características da Família , Serviços de Alimentação , Instituições Acadêmicas , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Estudos Cross-Over , Dinamarca , Avaliação Educacional , Feminino , Humanos , Masculino , Estado Nutricional , Fatores Sexuais , Resultado do Tratamento
8.
Biochim Biophys Acta ; 1258(3): 303-8, 1995 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-7548201

RESUMO

The formation of anandamide (N-arachidonoylethanolamine), N-acylethanolamine, and N-acylphosphatidylethanolamine was studied in primary cultures of rat cortical neurons. The cells were incubated for 22 h with [14C]ethanolamine, [U-14C]arachidonic acid, [3H]arachidonic acid, [32P]phosphate, [14C]stearic acid, or [3H]myristic acid. The lipids from the cells and media were separated by thin layer chromatography. [14C]Ethanolamine labelling revealed two compounds (I and II), which on different thin layer chromatography systems migrated as N-acylethanolamine (0.06-0.55% of total radioactivity) and N-acylphosphatidylethanolamine (0.66-6.49% of total radioactivity), respectively. Compound II was also labelled with [32P]phosphate, and radioactive fatty acids. Treatment of compound II with phospholipase D (Streptomyces chromofuscus) resulted in two compounds, one comigrating as phosphatidic acid and the other as N-acylethanolamine. Compound I could be labelled with [14C]stearic acid and [3H]myristic acid, but not with [3H]- or [14C]arachidonic acid. Exogenous [3H]anandamide was metabolised with a t1/2 of 2.6 h. The labelling of the two compounds identified as N-acylethanolamine and N-acylphosphatidylethanolamine were more pronounced the older the culture. The neurotoxic amino acid, glutamate, stimulated within 2 h dose-dependently (ED50 = 40 microM) the formation of both compounds. It is suggested that N-acylethanolamine and N-acylphosphatidylethanolamine are formed in relation to the cytotoxicity induced by glutamate, and that these compounds may be markers of neurotoxicity. We could not detect any formation of anandamide using radioactive arachidonic acid.


Assuntos
Etanolaminas/metabolismo , Ácido Glutâmico/farmacologia , Neurônios/efeitos dos fármacos , Fosfatidiletanolaminas/metabolismo , Animais , Ácido Araquidônico/metabolismo , Ácidos Araquidônicos/metabolismo , Morte Celular , Células Cultivadas , Córtex Cerebral/citologia , Cromatografia em Camada Fina , Endocanabinoides , Etanolamina , Neurônios/metabolismo , Alcamidas Poli-Insaturadas , Ratos
9.
Artigo em Inglês | MEDLINE | ID: mdl-26254087

RESUMO

Recent evidence suggests that the effects of n-3LCPUFA might be mediated through epigenetic mechanisms, especially DNA-methylation, during pregnancy and early life. A randomized trial was conducted in 133 9-mo-old, infants who received 3.8g/day of fish oil (FO) or sunflower oil (SO) for 9 mo. In a subset of 12 children, buffy-coat DNA was extracted before and after intervention and analyzed on Illumina-Human-Methylation 450-arrays to explore genome-wide differences between the FO and SO groups. Genome-wide-methylation analysis did not reveal significant differences between groups after adjustment for multiple testing. However, analysis of the top-ranked CpG-sites revealed 43 CpG׳s that appear modified with an absolute difference in methylation of ≥10%. Methylation levels at these sites were associated with phenotypic changes mainly in blood pressure. In conclusion, our analyses suggest potential epigenome effects that might be associated with functional outcomes, yet the effect sizes were small and should be verified by additional investigation.


Assuntos
Ilhas de CpG , Metilação de DNA/efeitos dos fármacos , Óleos de Peixe/administração & dosagem , Leucócitos Mononucleares/efeitos dos fármacos , Óleos de Plantas/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Suplementos Nutricionais , Método Duplo-Cego , Epigênese Genética/efeitos dos fármacos , Feminino , Óleos de Peixe/farmacologia , Genoma Humano , Humanos , Lactente , Masculino , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Projetos Piloto , Óleos de Plantas/farmacologia , Óleo de Girassol
10.
Artigo em Inglês | MEDLINE | ID: mdl-25753812

RESUMO

Fatty acid analysis requires standardized collection and storage of samples, which can be a challenge under field conditions. This study describes the effect of storage temperature on fatty acid composition in two sets of whole blood samples collected from 66 children in a rural area in Cambodia. The samples were stored with butylated hydroxytoluene at -20 °C and -80 °C and the latter required extra transfers due to storage facility limitation. Fatty acid composition was analyzed by high-throughput gas-chromatography and evaluated by paired t-tests and Bland-Altman plots. Total amounts of fat in -20 °C and -80 °C samples did not differ, but there was relatively more highly unsaturated fatty acids (15.8 ± 2.7 vs. 14.4 ± 2.5%, p < 0.001) and a lower n-6/n-3 ratio (6.4 ± 1.4 vs. 6.9 ± 1.4, p < 0.001) in the -20 °C samples. Our results indicate that the importance of storage temperature should be evaluated in the context of storage facility availability and risk of temperature fluctuations during transport.


Assuntos
Preservação de Sangue/métodos , Ácidos Graxos Ômega-3/sangue , Camboja , Humanos , Lactente , Temperatura
11.
Eur J Clin Nutr ; 69(5): 626-31, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25491500

RESUMO

BACKGROUND/OBJECTIVES: A nutritionally adequate diet in childhood is important for health and resistance of allergies and infections. This study explored the effects of school meals rich in fish, vegetables and fibre on school attendance, asthma, allergies and illness in 797 Danish 8- to 11-year-old children. No comparable studies conducted in high-income settings have been identified. SUBJECTS/METHODS: The OPUS School Meal Study was a cluster-randomised cross-over trial. Children from third and fourth grades at nine Danish schools received school meals or usual packed lunch (control) for two 3-month periods. Occurrence and duration of illnesses, asthma and allergies during the last 14 days were recorded by parental questionnaires at baseline and after each 3-month period. Self-reported well-being was assessed by visual analogue scales. RESULTS: The school meals did not affect school attendance, parent-reported occurrence or duration of asthma and allergies or self-reported well-being. The most common symptoms of illness were stomach pain (24%), headache (28%) and cold (24%). A slightly higher number of children experienced headaches in the school meal (27%) compared with the control period (22%) (P=0.02). However, subgroup analyses showed that this effect was only seen in children eating school meals in the classroom (P=0.007), and not in common dining areas (P=0.2). No effect was found on other symptoms of illness. CONCLUSIONS: Provision of nutritionally balanced school meals did not affect school attendance, asthma, allergies, illness or well-being in 8- to 11-year-old children. The slight increase in occurrence of headaches seems to be related to the physical eating environment.


Assuntos
Proteção da Criança/estatística & dados numéricos , Dieta/normas , Serviços de Alimentação/normas , Cefaleia/epidemiologia , Instituições Acadêmicas , Asma/epidemiologia , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Análise por Conglomerados , Estudos Cross-Over , Dinamarca/epidemiologia , Feminino , Cefaleia/etiologia , Humanos , Hipersensibilidade/epidemiologia , Almoço , Masculino , Refeições , Serviços de Saúde Escolar , Inquéritos e Questionários
12.
Biochem Pharmacol ; 55(6): 719-25, 1998 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-9586943

RESUMO

The formation of N-acyl-phosphatidylethanolamine (NAPE) and N-acylethanolamine (NAE), including anandamide, in mammals in relation to neurotoxicity is discussed. Data on the characterization of the NAPE-forming N-acyltransferase, the NAPE-hydrolyzing phospholipase D, and the NAE-hydrolyzing amidase are reviewed. We suggest that NAPE and NAE, including anandamide, are formed in neurons in response to the high intracellular calcium concentrations that occur in injured neurons, e.g. due to glutamate excitotoxicity. NAPE may have functions of its own besides being a precursor for NAE. The formation of both of these lipids may serve as a cytoprotective response, whether mediated by physical interactions with membranes or enzymes, or mediated by activation of cannabinoid receptors. This suggestion implies that NAPE and NAE may have pathophysiological roles in the brain. Whether these lipids also have physiological roles is uncertain.


Assuntos
Encéfalo/metabolismo , Citoproteção/fisiologia , Etanolaminas/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/metabolismo , Amidoidrolases/metabolismo , Animais , Encéfalo/citologia , Humanos , Hidrólise , Fosfolipase D/metabolismo
13.
Mol Cell Endocrinol ; 104(2): 229-35, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7988749

RESUMO

The results of the present study point to phosphatidic acid (PtdOH) as a possible intracellular messenger, which might be involved in local modulation of testicular testosterone production in vivo. Propranolol (27-266 microM) induced an increased level of [3H]PtdOH in isolated rat Leydig cells, prelabeled with [3H]myristate, and at the same time a strong dose-dependent inhibition of the acute testosterone production stimulated by luteinizing hormone (LH). The inhibition was not bypassed by the addition of dibutyryl-cAMP but was overcome, when 22(R)-hydroxycholesterol was added as a direct substrate for cytochrome P-450 side chain cleavage enzyme. Thus, the inhibition appears to be exerted at a point distal to cAMP-generation but before the first enzyme in the testosterone synthetic pathway. Treatment with other agents (4 beta-phorbol 12-myristate 13-acetate (PMA), A23187, and sphingosine) giving rise to increases in the PtdOH-level resulted in the inhibition of the LH-induced testosterone formation as well, thus indicating a connection between the two effects. Furthermore, we were able to demonstrate a highly significant correlation between the PtdOH-increase and the inhibition of the LH-stimulated testosterone production. This may suggest a causal relationship between these two parameters.


Assuntos
Células Intersticiais do Testículo/metabolismo , Hormônio Luteinizante/farmacologia , Ácidos Fosfatídicos/metabolismo , Propranolol/farmacologia , Testosterona/antagonistas & inibidores , Animais , Bucladesina/farmacologia , Calcimicina/farmacologia , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , AMP Cíclico/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Masculino , Ácido Mirístico , Ácidos Mirísticos/metabolismo , Fosfolipase D/metabolismo , Ratos , Ratos Sprague-Dawley , Esfingosina/farmacologia , Testosterona/biossíntese , Acetato de Tetradecanoilforbol/farmacologia
14.
Mol Cell Endocrinol ; 152(1-2): 99-110, 1999 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-10432228

RESUMO

Rat Leydig cells contain a phospholipase D (PLD), which can be activated by vasopressin and phorbol ester. In order to clarify which Leydig cell organelles that express PLD activity, the subcellular localization of two differently regulated PLD activities was investigated by subcellular fractionation on a 40% (v/v) self-generating Percoll gradient. PLD activities in broken cells were estimated using radiolabeled didecanoylphosphatidylcholine as a substrate. Initial experiments revealed the presence of an oleate Mg2+ -activated PLD and a phosphatidylinositol 4,5-bisphosphate-activated PLD (PIP2-PLD) in the microsomal fraction of Leydig cells. The latter activity could be further stimulated by recombinant nonmyristoylated ADP ribosylating factor 1 (ARF1) plus GTPgammaS. The peak of oleate Mg2+ -PLD activity colocalized with the plasma membrane marker, whereas the highest specific activity of the PIP2-PLD activity was found in fractions with a slightly lower density than those containing the plasma membrane and trans-Golgi marker enzymes. In order to localize phorbol ester-stimulated PLD activity in intact Leydig cells, the cells were prelabeled with [14C]-palmitate and then stimulated for 15 min with 100 nM 4-beta-phorbol-12-myristate-13-acetate (PMA) in the presence of ethanol or butanol. The PLD product [14C]-phosphatidylethanol, expressed as the percentage of total labeled phospholipids in the fraction, was slightly increased in all Percoll fractions and showed a prominent peak in the fractions containing plasma membrane, trans-Golgi, and fractions of slightly lower density. The PMA-induced formation of [14C]-phosphatidylbutanol could be inhibited dose-dependently with brefeldin A suggesting that the activation of PLD by the phorbol ester was mediated by ARF.


Assuntos
Células Intersticiais do Testículo/enzimologia , Fosfolipase D/metabolismo , Fator 1 de Ribosilação do ADP , Fatores de Ribosilação do ADP , Animais , Brefeldina A/farmacologia , Carcinógenos/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Glicerofosfolipídeos/metabolismo , Células Intersticiais do Testículo/ultraestrutura , Masculino , Organelas/metabolismo , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Proteínas Recombinantes/metabolismo , Acetato de Tetradecanoilforbol/farmacologia
15.
Psychopharmacology (Berl) ; 114(1): 119-22, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7846193

RESUMO

In a 6-week study the efficacy of combined treatment of imipramine plus mianserin was compared to combined treatment of desipramine plus mianserin in patients with post-stroke depression. Patients were required to have a minimum baseline total score of 15 on the 17-item Hamilton Depression Scale (HAMD). The Melancholia Scale (MES) was also used to measure severity of depressive states to show that somatic symptoms had little influence on the evaluation of depression. Out of 120 stroke patients screened, 20 patients fulfilled the inclusion criteria. The doses of the drugs were flexible, using side-effects as a guide during treatment. Both intention to treat analysis and efficacy data (excluding patients who had dropped out during the first 2 weeks of treatment) showed that imipramine (mean dose 75 mg daily) plus mianserin (mean dose 25 mg daily) was superior to desipramine (mean dose 66 mg daily) plus mianserin (27 mg daily). The MES was found to be more sensitive than the HAMD for measuring change in depressive states during treatment. The assessment of side-effects using the UKU scale showed good tolerance in general. The only difference between the two treatment groups was seen in micturition disturbances, where the imipramine treated patients had most complaints after 14 days of treatment, but the symptoms disappeared despite continuous treatment.


Assuntos
Transtornos Cerebrovasculares/complicações , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/etiologia , Desipramina/uso terapêutico , Imipramina/uso terapêutico , Mianserina/uso terapêutico , Idoso , Transtornos Cerebrovasculares/psicologia , Desipramina/administração & dosagem , Desipramina/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Imipramina/administração & dosagem , Imipramina/efeitos adversos , Masculino , Mianserina/administração & dosagem , Mianserina/efeitos adversos , Escalas de Graduação Psiquiátrica
16.
J Affect Disord ; 33(3): 143-50, 1995 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-7790665

RESUMO

A definite (anchored) and a semidefinite (semi-anchored) questionnaire version of the Hamilton Depression Rating Scale (HDS) and the Bech-Rafaelsen Melancholia Scale (MES) were compared with the HDS/MES by observer-rating and self-rating of 24 patients fulfilling the DSM-3R criteria for major depressive disorder. Both types of questionnaire showed substantial agreement with the observer scale from which they were derived. The sum scores were for the definite questionnaires and the corresponding observer scales closely similar whereas the sum scores of the semidefinite questionnaires were significantly higher than the sum scores of the corresponding observer scales. These results indicate that patients' 'halo' effect may be avoided by using definite scaling criteria for self-rating. Thus, of the two versions of questionnaires the definite versions are recommended.


Assuntos
Transtorno Depressivo/diagnóstico , Inventário de Personalidade/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Determinação da Personalidade/estatística & dados numéricos , Psicometria , Reprodutibilidade dos Testes
17.
J Affect Disord ; 18(1): 59-66, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2136870

RESUMO

The pretreatment plasma ratio of tryptophan (Trp) to other large neutral amino acids (LNAA), thought to reflect brain serotonin formation, was determined in 44 inpatients with major depression, who were subsequently treated double-blind on a fixed-dose schedule for 4 weeks with the selective serotonin uptake inhibitor paroxetine (n = 27) or clomipramine (n = 17). The study took place at four clinical centers. Endogenous and non-endogenous depressives were comparable with respect to the ratio Trp/LNAA and clinical improvement and were therefore analyzed together. The clomipramine group showed a significant inverse correlation between ratio Trp/LNAA and improvement, and patients with a ratio Trp/LNAA below the mean showed a trend towards greater improvement than patients with a higher ratio but with comparable serum drug levels. The improvement in the paroxetine group was significantly inversely correlated with the Trp concentration but not with the ratio Trp/LNAA. The findings accord with previous trials of various antidepressant treatments, in which about 25% of the variance in therapeutic response associates with pretreatment plasma amino acid profiles.


Assuntos
Clomipramina/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Piperidinas/uso terapêutico , Antagonistas da Serotonina/uso terapêutico , Triptofano/sangue , Adulto , Idoso , Aminoácidos/sangue , Ensaios Clínicos como Assunto , Transtorno Depressivo/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paroxetina
19.
Eur Psychiatry ; 11(4): 185-91, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-19698448

RESUMO

The paper discusses the relevance of sufficient psychometric standards for dementia rating scales. The concurrent, convergent and construct validity of the Mini Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale (ADAS) and the CAMCOG are assessed. The Clinical Global Impressions and the Global Deterioration Scale are used as global scales. The concurrent and convergent validity are satisfactory. The construct validity expressed by the Cronbach and Loevinger coefficient are very good for all scales and subscales. The Mokken's single item coefficients show that the MMSE has the best individual hierarchical fit, the item reading can be left out. The ADAS is less uni-dimensional, eight items can be left out. The CAMCOG consists of too many items to apply the Mokken's single item coefficients or the Loevinger coefficient. Instead, the CAMCOG subscales are analyzed. This results in a possible reduction of the CAMCOG by 30 items to a total of 35 items. The factor analysis reveals two factors in both the MMSE and the ADAS while the number of observations does not allow a factor analysis of the CAMCOG to be performed.

20.
Eur Psychiatry ; 12(8): 399-404, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-19698561

RESUMO

A study of 128 consecutive patients with thromboembolic stroke in a rehabilitation hospital from July 1988 to September 1990 found a prevalence of major depression of 17%. The patient population was described according to the principles of the World Health Organization's (WHO) International Classification of Impairments, Disabilities and Handicaps (ICIDH) according to biological impairment, measured by computerized tomography (CT) scanning of the brain and side of hemiparesis and physical disability, measured by functional movement and activities of daily living. Handicap, referring to the interaction between disability and the environmental situation, often defined as the subjective disadvantage of being ill, was not measured in this study. A stroke index with four items was generated from the parameters describing biological impairment and physical disability. The psychiatric rating scales (the 17-item Hamilton Scale for Depression (HAM-D), the Melancholia Scale [MES]and the Newcastle Diagnostic Depression Scale), and the new stroke-index showed adequate coefficients of Cronbach's alpha and Loevinger, suggesting that these scales have both adequate item correlation and homogeneity (adequate hierarchical structure). The impairment disability index of stroke thus seems to be a meaningful measurement of the specific factors of this disease. There was no correlation between the stroke-index and the psychiatric rating scales measuring the emotional dimension of disability caused by the disease expressed as depression. The results suggest that the depression found among stroke patients is not a simple reaction to the physical disability of the stroke.

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